image: Figure 1. Differential gene expression and directional overlap across comparison groups. (A) Numbers of annotated DEGs (FDR < 0.01 and |log2FC| ≥ 0.5) in spleen, liver and kidney across three comparisons: 1) old vs. young: wildtype control mice (22 months, n = 5) vs. young untreated 4F mice (3 months, n = 4); 2) reprogrammed vs. old: partially reprogrammed mice (22 months, n = 5) vs. wildtype control mice (22 months, n = 5); 3) reprogrammed vs. young: partially reprogrammed mice (22 months, n = 5) vs. untreated 4F mice (3 months, n = 4). (B) Directional overlap of DEGs across comparison groups. The tables show genes that are differentially expressed in both the comparison described by the row as well as in the comparison described by the column. Each cell counts genes that change in the specified directions; for example, intersecting “Upregulated DEGs old vs. young” with “Downregulated DEGs reprogrammed vs. old” counts genes that are upregulated with aging but downregulated with reprogramming. Background shading corresponds to the number of shared genes: None (0, white), Low (1–20, light blue), Moderate (21–100, medium blue), and High (>100, dark blue).
Credit: Copyright: © 2026 Meiners et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
“Our findings highlight tissue-specific responses to partial reprogramming and emphasize the need for larger, controlled studies to clarify physiological outcomes and safety.”
BUFFALO, NY — November 12, 2026 — A new research paper was published in Volume 18 of Aging on October 27, 2026, titled “Investigating the efficacy and toxicity of partial in vivo reprogramming as a rejuvenation intervention.”
The study examines how partial cellular reprogramming, an experimental approach aimed at reversing certain age-related changes, affects different organs. Researchers found potentially beneficial molecular changes in the liver and kidneys of aged mice, alongside signals in the spleen that raise concerns about the intervention's long-term safety.
The paper's first and corresponding author is Franziska Meiners, affiliated with the Institute for Biostatistics and Informatics in Medicine and Ageing Research at University Medical Center Rostock, Germany.
Partial reprogramming has emerged as a potential rejuvenation strategy by temporarily activating proteins known as Yamanaka factors. These proteins can alter gene activity and may help restore some youthful cellular characteristics. However, concerns remain about possible adverse effects, including uncontrolled cell proliferation and genomic instability.
To investigate these effects, the researchers reanalyzed previously published gene-expression data from the liver, kidneys and spleen of aged mice that had undergone seven months of partial reprogramming. They used the Adverse Outcome Pathway framework to examine molecular changes associated with potential benefits and risks.
The analysis revealed different responses across the three organs. In the liver and kidneys, partial reprogramming was associated with reduced expression of inflammation-related genes and increased expression of genes involved in metabolic pathways that typically decline with age.
In the liver, changes in fatty acid metabolism and energy regulation suggested a potentially protective response against processes associated with fatty liver disease. The kidneys also showed gene-expression patterns consistent with increased metabolic activity and reduced inflammatory signaling, suggesting that partial reprogramming may reverse certain aging-related molecular changes.
However, the spleen showed a different pattern. Researchers observed increased activity in pathways involved in cell division, DNA replication and DNA repair, alongside changes in immune-cell populations. These findings raised concerns about potential genomic instability and excessive cell proliferation, although they did not establish that tissue damage had occurred.
“While these findings are promising, further functional validation is necessary to confirm physiological impact.”
The findings highlight the importance of evaluating partial reprogramming across different tissues, as potentially beneficial changes in one organ may occur alongside unfavorable responses in another.
However, the study was based on a secondary analysis of gene-expression data from a relatively small number of mice. The results do not demonstrate rejuvenation or toxicity in humans, and larger controlled studies are needed to assess functional outcomes and long-term safety.
Overall, the research provides new insights into the tissue-specific benefits and potential risks of partial reprogramming. Understanding these differences could help guide future efforts to develop safer and more effective rejuvenation interventions.
Paper DOI: https://doi.org/10.18632/aging.206431
Corresponding author: Franziska Meiners - franziska.meiners@uni-rostock.de
Abstract video: https://www.youtube.com/watch?v=hH518dZDq88
Keywords: partial reprogramming, aging, rejuvenation, adverse outcome pathways, metabolism
Click here to sign up for free Altmetric alerts about this article.
______
To learn more about the journal, please visit www.Aging-US.com and connect with us on social media:
- Bluesky
- ResearchGate
- X
- YouTube
- Spotify, and available wherever you listen to podcasts
Click here to subscribe to Aging publication updates.
For media inquiries, please contact media@impactjournals.com.
Journal
Aging-US
Method of Research
News article
Subject of Research
Cells
Article Title
Investigating the efficacy and toxicity of partial in vivo reprogramming as a rejuvenation intervention
Article Publication Date
27-Oct-2026
COI Statement
R.A.A., G.F., D.P. are shareholders of a company (Sustayn Bioscience GmbH) that may offer services related to analyzing cellular reprogramming data. F.M. has been employed by Sustayn Bioscience GmbH since August 2026. The remaining authors declare no competing interests.